cGMP plays an important role as a second messenger in intracellular signal transduction. An inhibitor of cGMP-specific PDE, an enzyme which degrades cGMP, increases the concentration of intracellular cGMP, enhances the effects of endothelium-derived relaxing factor (EDRF), nitro vasodilator or atrial natriuretic peptide, shows the anti-platelet activity, the anti-vasocontraction activity and the vasodilating activity, and are useful for treating cardiovascular diseases such as thrombosis, angina pectoris, hypertension, congestive heart failure, post-PTCA restenosis, peripheral vascular diseases, arterial sclerosis etc., inflammatory allergic diseases such as bronchitis, chronic asthma, allergic asthma, allergic coryza etc., alimentary canal diseases such as irritable intestine syndrome etc., glaucoma, impotence and the like. The PDE inhibitory activity and the adenosine receptor antagonistic activity of imidazo[4,5-g]quinazoline derivatives are described in J. Med. Chem., 29, 972 (1986), J. Med. Chem., 32, 2247 (1989), J. Org. Chem., 51, 616 (1986) and the references cited therein. However, these compounds are neither particularly strong PDE inhibitors nor selective cGMP-specific PDE inhibitors.
Further, 8-anilino-2,3-dihydro-1H-imidazo[4,5-g]quinazoline-2-one derivatives are disclosed in EP635507. However, a substituent at 8-position in the compounds described in EP635507 is limited to an anilino group. Further, there is no description in EP635507 of the PDE inhibitory activity of the compounds.
In addition, 2,3-dihydro-1H-imidazo[4,5-g]quinazoline derivatives with cCMP-specific PDE inhibitory activity are disclosed in WO95/06648. However, in the case where a substituent at the 8-position in the compounds in WO95/06648 is aralkyl, a substituent in the aryl moiety of said aralkyl is limited to dialkyl-substituted amino such as dimethyl amino etc., lower alkyl, lower alkoxy, halogen and trifluoromethyl. There is no description therein of those compounds where the substituent in the aryl moiety of the aralkyl is monoalkyl-substituted amino or those compounds having cyclic amino groups such as morpholino, piperidino and thiomorpholino.
The PDE inhibitors known so far inhibit not only cGMP-specific PDE but also the cyclic adenosine 3',5'-monophosphate (cAMP) specific PDE which is an enzyme similar thereto, and therefore causes the elevation of the concentration of cAMP as well as intracellular cGMP and may cause side effects and the like. Further, the inhibitory activities thereof are not yet sufficient, and compounds which are more potent and selective are expected and desired.